Various publications, such as U.S. Pat. Nos. 3,615,024 and 3,691,068, and German laid-open application (DE-OS) No. 2,917,357, disclose hollow fibers and other membranes comprising a hydrophobic polymer. Such membranes, which are intended to be suitable for use in the hemodialysis, hemodiafiltration and hemofiltration of blood, cannot be wetted in the dry condition with water, so that they may either not be entirely dried, or they must be filled with a hydrophilic fluid, such as glycerin.
In order to eliminate the disadvantages of these requirements, and to improve the wettability, blood compatibility and diffusive permeability of these membranes, it is known to combine the hydrophobic polymers in the membrane with hydrophilic polymers, e.g., in European laid-open application Nos. 0,082,443; 0,168,782; and 0,305,787. In that respect, the hydrophobic polymers used are, for example, polysulphones, polyethersulphones, polycarbonates, polyaramides, polyamides, polyvinyl chloride, modified acrylic acid, polyethers, polyurethanes, polyacrylonitrile, polypropylene, polyetherimides, and copolymers thereof. In accordance with the above-mentioned patent specifications, the hydrophilic polymers used are polyvinylpyrrolidone, polyethyleneglycol, polyglycolmonoester, copolymers of polyethyleneglycol and polypropyleneglycol, cellulose derivatives, polysorbate and polyethylene-polypropyleneoxide copolymers. Polyvinylpyrrolidone is preferably used as the hydrophilic polymer.
Membranes of that type, in comparison with hydrophobic membranes, have the advantage of improved wettability with aqueous solutions, enhanced blood compatibility, and increased levels of diffusive permeability. There is, however, the problem that such membranes, upon reworking and use, gradually give off proportions of the hydrophilic polymer component, which, on the one hand, therefore results in a loss of the hydrophilic properties of the members; and, on the other hand, in medical use in vivo results in accumulation of the hydrophilic component, in particular polyvinylpyrrolidone, in the tissue of the patients.
In order to eliminate these disadvantages of hydrophilic membranes, the process of European laid-open application No. 0,261,734 immobilizes the hydrophilic polymer, such as polyvinylpyrrolidone, by cross-linking with heat treatment. Another known procedure is the cross-linking of polyvinylpyrrolidone with gel formation; for example, by irradiation with gamma rays. In that respect attention is directed, for example, to Macromol. Sci. Phys., B7 (2), pp. 209-244 (1973) . Also known is cross-linking by UV-irradiation (Poly. Sci. USSR, 11, p. 1638 [1968]) and chemical cross-linking (Tetrahedron, 19, pp. 1441-1454 [1963]).
In Journal of Applied Polymer Science 23, 2453 (1979) , the mechanism of cross-linking for PVP in solution with persulphate is disclosed as a radial reaction. Cross-linking is achieved by combining two macroradicals resulting in a polymeric gel which is virtually insoluble in the swollen condition. In this cross-linking reaction undesired byproducts are produced which may have reduced hemocompatibility. It has been found that OH-groups on surfaces of membranes produced in the known manner are contributing to increased complement activation in comparison with surfaces with OH-groups.
It is therefore the underlying object of the present invention to provide without undesired byproducts a process for the production of hydrophilic membranes using polyvinylpyrrolidone as a hydrophilic polymer, which give off the minimum amount (or none) of polyvinylpyrrolidone by virtue of extraction, and which exhibit improved efficiency.